17: Cancer Causes Control 1991 Nov;2(6):427-42 Vegetables, fruit, and cancer. II. Mechanisms. Steinmetz KA, Potter JD. Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55455. The epidemiologic literature on the relationship between vegetable and fruit consumption and human cancer at a variety of sites was reviewed systematically in Part I. It was concluded that consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites, and particularly with epithelial cancers of the alimentary and respiratory tracts. Possible mechanisms by which vegetable and fruit intake might alter risk of cancer are addressed here. A large number of potentially anticarcinogenic agents are found in these food sources, including carotenoids, vitamins C and E, selenium, dietary fiber, dithiolthiones, glucosinolates and indoles, isothiocyanates, flavonoids, phenols, protease inhibitors, plant sterols, allium compounds, and limonene. These agents have both complementary and overlapping mechanisms of action, including the induction of detoxification enzymes, inhibition of nitrosamine formation, provision of substrate for formation of antineoplastic agents, dilution and binding of carcinogens in the digestive tract, alteration of hormone metabolism, antioxidant effects, and others. It appears extremely unlikely that any one substance is responsible for all the associations seen. Possible adverse effects of vegetable and fruit consumption are also examined. One way to consider the relationships reviewed here is to hypothesize that humans are adapted to a high intake of plant foods that supply substances crucial to the maintenance of the organism, but only some of which are currently called 'essential nutrients.' Cancer may be the result of reducing the level of intake of foods that are metabolically necessary--it may be a disease of maladaptation. [ed.: !!] Publication Types: Review Review, academic PMID: 1764568 [PubMed - indexed for MEDLINE]
16: IARC Sci Publ 1996;(139):61-90 Vegetables, fruit and phytoestrogens as preventive agents. Potter JD, Steinmetz K. Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. The practice of medicine-both past and present-often involves the prescription of specific foods (almost always plants) or their potent derivatives, to treat a wide spectrum of illnesses. Foods that have been ascribed healing properties include the Cruciferae, the allium family, celery, cucumber, endive, parsley, radish and legumes. Review of the epidemiological data, including both cohort and case-control studies, of all cancer sites strongly suggests that plant foods also have preventive potential and that consumption of the following groups and types of vegetables and fruits is lower in those who subsequently develop cancer: raw and fresh vegetables, leafy green vegetables, Cruciferae, carrots, broccoli, cabbage, lettuce, and raw and fresh fruit (including tomatoes and citrus fruit). Other data suggest that foods high in phytoestrogens, particularly soy (which contains isoflavones), or high in precursor compounds that can be metabolized by gut bacteria into active agents, particularly some grains and vegetables with woody stems (which contain precursors to lignans), are plausibly associated with a lower risk of sex-hormone-related cancers. The human evidence for these latter associations is not strong. There are many biologically plausible reasons why consumption of plant foods might slow or prevent the appearance of cancer. These include the presence in plant foods of such potentially anticarcinogenic substances as carotenoids, vitamin C, vitamin E, selenium, dietary fibre (and its components), dithiolthiones, isothiocyanates, indoles, phenols, protease inhibitors, allium compounds, plant sterols, and limonene. Phytoestrogens are also derived from some vegetables and berries as well as grains and seeds. Most of the data for the observations on the anticarcinogenic potential of all of these compounds have come from animal and in vitro studies. At almost every one of the stages of the cancer process, identified phytochemicals are known to be able to alter the likelihood of carcinogenesis-occasionally in a way that enhances risk but usually in a favourable direction. For example, glucosinolates and indoles, thiocyanates and isothiocyanates, phenols, and coumarins can induce a multiplicity of phase II (solubilizing and usually inactivating) enzymes; ascorbate and phenols block the formation of carcinogens such as nitrosamines; flavonoids and carotenoids act as antioxidants, essentially disabling the carcinogenic potential of specific compounds; lipid-soluble compounds such as carotenoids and sterols may alter membrane structure or integrity; some sulphur-containing compounds suppress DNA and protein synthesis; carotenoids can suppress DNA synthesis and enhance differentiation; and phytoestrogens compete with estradiol for estrogen receptors in a way that is generally antiproliferative. Consumption of diets low in plant foods results in a reduced intake of a wide variety of those substances that can plausibly lower cancer risk. In the presence of a diet and lifestyle high in potential carcinogens (whether derived from fungal contamination, cooking or tobacco) or high in promoters (such as salt and alcohol), overall risk of cancer at many epithelial sites is elevated. Plant foods appear to exert a general risk-lowering effect; the patterns of exposure to cancer initiators and promoters and of genetic susceptibility may determine the variations in the site-specific risks of cancer seen across populations. Publication Types: Review Review, tutorial PMID: 8923020 [PubMed - indexed for MEDLINE]
4: Nutr Cancer 2000;36(2):224-9 Inhibition of azoxymethane-induced colon cancer by orange juice. Miyagi Y, Om AS, Chee KM, Bennink MR. Michigan State University, East Lansing 48824-1224, USA. Previous research has shown that hesperidin, a flavanone glycoside in orange juice, inhibits colon carcinogenesis and that feeding double-strength orange juice delays the onset of chemically induced mammary cancer in rats. This study determined whether feeding single-strength, pasteurized orange juice would inhibit azoxymethane (AOM)-induced colon cancer in male Fischer 344 rats. Colon cancer was initiated by injecting AOM (15 mg/kg body wt) at 22 and 29 days of age. One week after the second AOM injection, orange juice replaced drinking water for the experimental group (n = 30). The rats were killed 28 weeks later, and tumors were removed for histological analysis. Feeding orange juice reduced tumor incidence by 22% (p < 0.05). Tumor reduction was associated with a decreased labeling index and proliferation zone in the colonic mucosa. Hesperidin, other flavonoids, limonin 17-beta-D-glucopyranoside, and other limonoid glucosides are potential chemopreventive agents in orange juice that could account for the decreased colon tumorigenesis associated with feeding orange juice. PMID: 10890034 [PubMed - indexed for MEDLINE]
1: J Agric Food Chem 2001 Feb;49(2):1035-41 In vitro availability of flavonoids and other phenolics in orange juice. Gil-Izquierdo A, Gil MI, Ferreres F, Tomas-Barberan FA. Departamento de Ciencia y Tecnologia de Alimentos, CEBAS (CSIC), P.O. Box 4195, 30080 Murcia, Spain. Hand-squeezed navel orange juice contains 839 mg/L phenolics, including flavanones, flavones, and hydroxycinnamic acid derivatives. The flavanones are the main phenolics in the soluble fraction (648.6 mg/L) and are also present in the cloud fraction (104.8 mg/L). During refrigerated storage of fresh juice (4 degrees C), 50% of the soluble flavanones precipitate and integrate into the cloud fraction. Commercial orange juices contain only 81-200 mg/L soluble flavanones (15-33%) and the content in the cloud is higher (206-644 mg/L) (62-85%), showing that during industrial processing and storage the soluble flavanones precipitate and are included in the cloud. An in vitro simulation of orange juice digestion shows that a serving of fresh orange juice (240 mL) provides 9.7 mg of soluble hesperidin (4'-methoxy-3',5,7-trihydroxyflavanone-7-rutinoside) and 4.7 mg of the C-glycosylflavone vicenin 2 (apigenin, 6,8-di-C-glucoside) for freshly squeezed orange juice, whereas pasteurized commercial juices provide 3.7 mg of soluble hesperidin and a higher amount of vicenin 2 (6.3 mg). This means that although orange juice is a very rich source of flavanones, only a limited quantity is soluble, and this might affect availability for absorption (11-36% of the soluble flavanones, depending on the juice). The flavanones precipitated in the cloud are not available for absorption and are partly transformed to the corresponding chalcones during the pancreatin-bile digestion. PMID: 11262068 [PubMed - indexed for MEDLINE]
5: Curr Med Chem 2001 Feb;8(2):135-53 Biological properties of citrus flavonoids pertaining to cancer and inflammation. Manthey JA, Grohmann K, Guthrie N. US Citrus and Subtropical Products Laboratory, USDA, ARS, SAA, 600 Avenue S, NW, Winter Haven, FL 33881, USA. jmanthey@citrus.usda.gov Citrus flavonoids encompass a diverse set of structures, including numerous flavanone and flavone O- and C-glycosides and methoxylated flavones. Each of these groups of compounds exhibits a number of in vitro and in vivo anti-inflammatory and anticancer actions. These biological properties are consistent with their effects on the microvascular endothelial tissue. Evidence suggests that the biological actions of the citrus flavonoids are possibly linked to their interactions with key regulatory enzymes involved in cell activation and receptor binding. The citrus flavonoids show little effect on normal, healthy cells, and thus typically exhibit remarkably low toxicity in animals. The citrus flavonoids extend their influence in vivo through their induction of hepatic phase I and II enzymes, and through the biological actions of their metabolites. Evidence clearly indicates to the potential health promoting properties of these dietary compounds. Publication Types: Review Review, academic PMID: 11172671 [PubMed - indexed for MEDLINE]
8: MMW Fortschr Med 1999 Sep 23;141(38):40-3 [New knowledge about cancer and nutrition. 5 servings of fruit and vegetables per day prevent cancer]. [Article in German] Zurcher G. Sektion Ernahrungsmedizin u. Diatetik, Medizinischen Universitatsklinik Freiburg. On average, lacto-ovo-vegetarians develop cancer less often than their meat-eating fellows. A particularly clear correlation exists between vegetable consumption and the reduction of the risk of developing cancer of the gastrointestinal tract or lung cancer. The factors responsible for the anticarcinogenic effects are not vitamins, minerals and ballast (fiber) alone, but also include in particular the secondary plant substances, whose numbers run into thousands. These substances act in a variety of different ways--for example carotinoids and flavonoids inhibit carcinogen-activating enzymes, phyto-estrogens and indoles have a modulating effect on the hormone metabolism, while saponins or sulfides stimulate the body's natural killer cells. Against this background, the German Society for Nutrition (Deutsche Gesellschaft fur Ernahrung) recommends the daily consumption of 375 grams of vegetables and about 250 to 300 grams of fruit. Publication Types: Review Review, tutorial PMID: 10904615 [PubMed - indexed for MEDLINE]
13: J Am Diet Assoc 1996 Oct;96(10):1027-39 Vegetables, fruit, and cancer prevention: a review. Steinmetz KA, Potter JD. World Cancer Research Fund, London, England. In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented. Publication Types: Review Review, academic PMID: 8841165 [PubMed - indexed for MEDLINE]
12: Am J Clin Nutr 1999 Jan;69(1):87-94 Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Young JF, Nielsen SE, Haraldsdottir J, Daneshvar B, Lauridsen ST, Knuthsen P, Crozier A, Sandstrom B, Dragsted LO. Research Department of Human Nutrition, Nutrition, Royal Veterinary and Agricultural University, Frederiksberg, Denmark. BACKGROUND: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. OBJECTIVE: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers of oxidative status. DESIGN: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL) consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin/d. RESULTS: Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was 0.29-0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention because of the ascorbate in the juice. Total plasma malondialdehyde decreased with time during the 1500-mL juice intervention, indicating reduced lipid oxidation in plasma. Plasma 2-amino-adipic semialdehyde residues increased with time and dose, indicating a prooxidant effect of the juice, whereas erythrocyte 2-aminoadipic semialdehyde and gamma-glutamyl semialdehyde concentrations, Trolox-equivalent antioxidant capacity, and ferric reducing ability of plasma did not change. Glutathione peroxidase activity increased significantly with juice dose. CONCLUSIONS: Urinary excretion of quercetin seemed to be a small but constant function of quercetin intake. Short-term, high intake of black currant and apple juices had a prooxidant effect on plasma proteins and increased glutathione peroxidase activity, whereas lipid oxidation in plasma seemed to decrease. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content. Publication Types: Clinical trial Randomized controlled trial PMID: 9925128 [PubMed - indexed for MEDLINE]
1: Carcinogenesis 2001 Feb;22(2):351-6 Inhibition of cellular transformation by berry extracts. Xue H, Aziz RM, Sun N, Cassady JM, Kamendulis LM, Xu Y, Stoner GD, Klaunig JE. Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA. Recent studies have examined and demonstrated the potential cancer chemopreventive activity of freeze-dried berries including strawberries and black raspberries. Although ellagic acid, an abundant component in these berries, has been shown to inhibit carcinogenesis both in vivo and in vitro, several studies have reported that other compounds in the berries may also contribute to the observed inhibitory effect. In the present study, freeze-dried strawberries (Fragara ananassa, FA) or black raspberries (Rubus ursinus, RU) were extracted, partitioned and chromatographed into several fractions (FA-F001, FA-F003, FA-F004, FA-F005, FA-DM, FA-ME from strawberries and RU-F001, RU-F003, RU-F004, RU-F005, RU-DM, RU-ME from black raspberries). These extracts, along with ellagic acid, were analyzed for anti-transformation activity in the Syrian hamster embryo (SHE) cell transformation model. None of the extracts nor ellagic acid by themselves produced an increase in morphological transformation. For assessment of chemopreventive activity, SHE cells were treated with each agent and benzo[a]pyrene (B[a]P) for 7 days. Ellagic acid, FA-ME and RU-ME fractions produced a dose-dependent decrease in transformation compared with B[a]P treatment only, while other fractions failed to induce a significant decrease. Ellagic acid, FA-ME and RU-ME were further examined using a 24 h co-treatment with B[a]P or a 6 day treatment following 24 h with B[a]P. Ellagic acid showed inhibitory ability in both protocols. FA-ME and RU-ME significantly reduced B[a]P-induced transformation only when co-treated with B[a]P for 24 h. These results suggest that a methanol extract from strawberries and black raspberries may display chemopreventive activity. The possible mechanism by which these methanol fractions (FA-ME, RU-ME) inhibited cell transformation appear to involve interference of uptake, activation, detoxification of B[a]P and/or intervention of DNA binding and DNA repair. PMID: 11181460 [PubMed - indexed for MEDLINE]
2: Cancer Lett 1999 Mar 1;136(2):215-21 p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW. Cancer Prevention Program, Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA. bhagavati@musc.edu Ellagic acid is a phenolic compound present in fruits and nuts including raspberries, strawberries and walnuts. It is known to inhibit certain carcinogen-induced cancers and may have other chemopreventive properties. The effects of ellagic acid on cell cycle events and apoptosis were studied in cervical carcinoma (CaSki) cells. We found that ellagic acid at a concentration of 10(-5) M induced G arrest within 48 h, inhibited overall cell growth and induced apoptosis in CaSki cells after 72 h of treatment. Activation of the cdk inhibitory protein p21 by ellagic acid suggests a role for ellagic acid in cell cycle regulation of cancer cells. PMID: 10355751 [PubMed - indexed for MEDLINE]
6: J Agric Food Chem 2001 Jan;49(1):308-14 Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. Hwang J, Hodis HN, Sevanian A. Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA. julianah@hsc.usc.edu Postmenopausal women have an increased risk of coronary heart disease. Oxidation of low-density lipoprotein (LDL) has been implicated in atherogenesis, and the presence of modified LDL (LDL(-)) in plasma appears to represent LDL oxidation in vivo. Because previous studies have demonstrated a strong antiatherogenic effect of estrogen due to its antioxidant activity and similar antioxidant activity was found for specific isoflavones derived from soy extract, the antioxidant activity of a phytoestrogen extract derived from soy and alfalfa was studied. Copper-mediated LDL oxidation was inhibited in the presence of soy and alfalfa extracts, and this effect was further enhanced in the presence of acerola cherry extract, which is rich in ascorbic acid. Male rabbit aortic endothelial cells pretreated with soy extract were resistant to the toxic effects of high levels of LDL and LDL(-), and a lesser, but significant protection, was also afforded by alfalfa extract. Cell-mediated oxidation of LDL, measured by LDL(-) formation, was inhibited in the presence of soy extract but not alfalfa extract. However, in the presence of acerola cherry extract, both soy and alfalfa extracts potently inhibited the formation of LDL(-). These findings show that acerola cherry extract can enhance the antioxidant activity of soy and alfalfa extracts in a variety of LDL oxidation systems. The protective effect of these extracts is attributed to the presence of flavonoids in soy and alfalfa extracts and ascorbic acid in acerola cherry extract, which may act synergistically as antioxidants. It is postulated that this synergistic interaction among phytoestrogens, flavonoids, and ascorbic acid is due to the "peroxidolitic" action of ascorbic acid, which facilitates the copper-dependent decomposition of LDL peroxides to nonradical products; this synergy is complemented by a mechanism in which phytoestrogens stabilize the LDL structure and suppress the propagation of radical chain reactions. The combination of these extracts markedly lowers the concentrations of phytoestrogens required to achieve significant antioxidant activity toward LDL. PMID: 11170593 [PubMed - indexed for MEDLINE]
7: J Nutr 2000 Aug;130(8S Suppl):2073S-85S Dietary intake and bioavailability of polyphenols. Scalbert A, Williamson G. Laboratoire des Maladies Metaboliques et Micronutriments, INRA, 63122 Saint-Genes-Champanelle, France. The main dietary sources of polyphenols are reviewed, and the daily intake is calculated for a given diet containing some common fruits, vegetables and beverages. Phenolic acids account for about one third of the total intake and flavonoids account for the remaining two thirds. The most abundant flavonoids in the diet are flavanols (catechins plus proanthocyanidins), anthocyanins and their oxidation products. The main polyphenol dietary sources are fruit and beverages (fruit juice, wine, tea, coffee, chocolate and beer) and, to a lesser extent vegetables, dry legumes and cereals. The total intake is approximately 1 g/d. Large uncertainties remain due to the lack of comprehensive data on the content of some of the main polyphenol classes in food. Bioavailability studies in humans are discussed. The maximum concentration in plasma rarely exceeds 1 microM after the consumption of 10-100 mg of a single phenolic compound. However, the total plasma phenol concentration is probably higher due to the presence of metabolites formed in the body's tissues or by the colonic microflora. These metabolites are still largely unknown and not accounted for. Both chemical and biochemical factors that affect the absorption and metabolism of polyphenols are reviewed, with particular emphasis on flavonoid glycosides. A better understanding of these factors is essential to explain the large variations in bioavailability observed among polyphenols and among individuals. Publication Types: Review Review, tutorial PMID: 10917926 [PubMed - indexed for MEDLINE]
9: QJM 1999 Sep;92(9):527-30 Interaction of dietary antioxidants in vivo: how fruit and vegetables prevent disease? Eastwood MA. Department of Medicine, University of Edinburgh, Western General Hospital Trust, UK. Epidemiological studies indicate that fruit and vegetables are health-promoting and protective against disease, particularly cardiovascular disease and cancer. Possible plant nutrients providing this protection include antioxidants and dietary fibre. Clinical trials with antioxidant supplements give inconsistent results for protection against lung cancer in smokers, invasive cervical cancer, oesophageal and gastric cancers, colorectal polyps and coronary heart disease. The antioxidants used in trials may be contributing to a more complex system. Antioxidants have differing solubilities which partition across the phases of tissues, cells and macromolecular structures: water-soluble ascorbate, glutathione and urate; lipid-soluble tocopherols and carotenoids, and intermediatory-soluble flavonoids and hydroxycinnamic acids. The health protection provided by fruit and vegetables could arise through an integrated reductive environment delivered by plant antioxidants of differing solubility in each of the tissue, cellular and macromolecular phases. Publication Types: Review Review, tutorial PMID: 10627873 [PubMed - indexed for MEDLINE]
11: Food Chem Toxicol 1999 Sep-Oct;37(9-10):937-42 Dietary flavonoids: intake, health effects and bioavailability. Hollman PC, Katan MB. Wageningen Centre for Food Sciences, State Institute for Quality Control of Agricultural Products (RIKILT-DLO), The Netherlands. Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Over 4000 different flavonoids have been described. They may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumour development in animal studies. An estimation of the total flavonoid intake is difficult, because only limited data on food contents are available. It is estimated that humans ingest a few hundreds of milligram per day. The average intake of the subclasses of flavonols and flavones in The Netherlands was 23 mg/day. The intake of flavonols and flavones was inversely associated with subsequent coronary heart disease in most but not all prospective epidemiological studies. A protective effect of flavonols on cancer was found in only one prospective study. Flavonoids present in foods were considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). Flavonol glycosides might contribute to the antioxidant defences of blood. Dietary flavonols and flavones probably do not explain the cancer-protective effect of vegetables and fruits; a protective effect against cardiovascular disease is not conclusive. PMID: 10541448 [PubMed - indexed for MEDLINE]
14: Clin Pharmacol Ther 1996 Jul;60(1):34-40 Flavanone absorption after naringin, hesperidin, and citrus administration. Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Food Science and Human Nutrition Department, University of Florida, Gainesville. Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion. PMID: 8689809 [PubMed - indexed for MEDLINE]
15: Arch Intern Med 1996 Mar 25;156(6):637-42 Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Keli SO, Hertog MG, Feskens EJ, Kromhout D. Department of Chronic Disease and Environmental Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands. BACKGROUND: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. METHODS: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. RESULTS: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84). CONCLUSION: The habitual intake of flavonoids and their major source (tea) may protect against stroke. PMID: 8629875 [PubMed - indexed for MEDLINE]
4: Cancer Res 1998 Feb 1;58(3):442-7 Calcium and fructose intake in relation to risk of prostate cancer. Giovannucci E, Rimm EB, Wolk A, Ascherio A, Stampfer MJ, Colditz GA, Willett WC. Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. Laboratory and clinical data indicate an antitumor effect of 1,25(OH)2 vitamin D (1,25(OH)2D) on prostate cancer. High calcium intake suppresses formation of 1,25(OH)2D from 25(OH)D, thereby decreasing the 1,25(OH)2D level. Ingestion of fructose reduces plasma phosphate transiently, and hypophosphatemia stimulates 1,25(OH)2D production. We thus conducted a prospective study among 47,781 men of the Health Professionals Follow-Up Study free of cancer in 1986 to examine whether calcium and fructose intake influenced risk of prostate cancer. Between 1986 and 1994, 1369 non-stage A1 and 423 advanced (extraprostatic) cases of prostate cancer were diagnosed. Higher consumption of calcium was related to advanced prostate cancer [multivariate relative risk (RR), 2.97; 95% confidence interval (CI), 1.61-5.50 for intakes > or = 2000 mg/day versus < 500 mg/day; P, trend, 0.002] and metastatic prostate cancer (RR, 4.57; CI, 1.88-11.1; P, trend, <0.001). Calcium from food sources and from supplements independently increased risk. High fructose intake was related to a lower risk of advanced prostate cancer (multivariate RR, 0.51; CI, 0.33-0.80, for intakes > 70 versus [ or = 40 g/day; P, trend, 0.007). Fruit intake was inversely associated with risk of advanced prostate cancer (RR, 0.63; 95% CI, 0.43-0.93; for > 5 versus < or = 1 serving per day), and this association was accounted for by fructose intake. Non-fruit sources of fructose similarly predicted lower risk of advanced prostate cancer. A moderate positive association between energy-adjusted fat intake and advanced prostate cancer was attenuated and no longer statistically significant when controlled for calcium and fructose. Our findings provide indirect evidence for a protective influence of high 1,25(OH)2D levels on prostate cancer and support increased fruit consumption and avoidance of high calcium intake to reduce the risk of advanced prostate cancer. PMID: 9458087 [PubMed - indexed for MEDLINE]
1: Cancer Invest 2000;18(7):664-9 A medical hypothesis: phosphorus balance and prostate cancer. Kapur S. Deendayal Research Institute, New Delhi, India. Over the last three decades the mortality rate for prostatic carcinoma has steadily increased. Carcinoma of prostate (CaP), the most common malignancy in men, is also the second most common cause of cancer deaths in men. However, few epidemiologic studies have been done, and there are scant clues to the etiology/pathogenesis of CaP. As treatment failures for advanced carcinoma continue to frustrate clinicians, more emphasis has recently been focused on strategies to prevent invasive CaP. Prostatic hyperplasia is a universal phenomenon in aging men. Mechanism and signals causing this growth are not understood. Thus, prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have benign prostatic hyperplasia, of which some progress to CaP. Data from several studies support that higher levels of active metabolite of vitamin D, 1,25-(OH)2-D, reduce the risk of prostatic hyperplasia and CaP. Men with high serum levels of 1,25-(OH)2-D have a reduced risk of poorly differentiated and clinically advanced CaP. Receptor for vitamin D has been reported in both normal and cancer prostate cells. 1,25-(OH)2-D inhibits proliferation and induces differentiation of normal and neoplastic cells. Hypercalcemic activity of 1,25-(OH)2-D or its analogues, however, thwart their use for therapy in humans. 1,25-(OH)2-D also has an established role in phosphorus homeostasis. Low dietary intake of phosphorus leads to an increase in serum concentration of 1,25-(OH)2-D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr due to a rapid shift of phosphate from extracellular to intracellular compartment. Fruit intake has been shown to be associated with reduced risk of CaP, particularly the advanced type. Put together, these observations support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1,25-(OH)2-D, could reduce the risk of aging men to develop prostatic diseases, both benign prostatic hyperplasia and CaP. Publication Types: Review Review, tutorial PMID: 11036473 [PubMed - indexed for MEDLINE]
2: Indian J Exp Biol 1999 Jul;37(7):623-6 Phosphorus balance and prostate cancer. Kapur S. Ranbaxy Research Laboratory, New Delhi, India. Prostatic diseases affect men over the age of 45 and increase in frequency with age so that by the eighth decade more than 90% of men have Benign Prostatic Hyperplasia, (BPH), of which some progress to Carcinoma of Prostate (CaP). CaP, the most common malignancy in men, is also the second most common cause of death in men. Over the last three decades the mortality rate for CaP has steadily increased. There, however, are scant clues to the aetiology/pathogenesis of CaP. As treatment failures of advanced carcinoma continue to frustrate clinicians, emphasis has recently been focused on possible preventive strategies. Several studies support the view that higher levels of 1,25-(OH)2D, the active metabolite of vitamin D, reduce the risk of BPH and CaP. Men with high serum levels of 1,25-(OH)2D have a reduced risk of poorly differentiated and clinically advanced CaP. Hypercalcemic activity of 1,25-(OH)2D or its analogues, however, thwart their use for therapy in humans. Incidentally, a low dietary intake of phosphorus has been reported to increase serum levels of 1,25-(OH)2D. In addition, dietary fructose reduces plasma phosphate levels by 30 to 50% for more than 3 hr. Fruit intake has, indeed, been shown to be associated with reduced risk of CaP, particularly the advanced type. These observations, taken together, support that dietary determinants of hypophosphatemia, leading to increased plasma levels of 1,25-(OH)2D, could reduce the risk of ageing men to develop prostatic diseases, both BPH and/or carcinoma of Prostate. Publication Types: Review Review, tutorial PMID: 10522150 [PubMed - indexed for MEDLINE]
3: Semin Cancer Biol 1998 Aug;8(4):263-73 What causes prostate cancer? A brief summary of the epidemiology. Chan JM, Stampfer MJ, Giovannucci EL. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. In recent decades, prostate cancer has emerged as one of the most common diseases among older men, particularly in Western society. Several years ago, only age, race, and family history were known risk factors for this disease. However, today, much progress has been made towards discovering nutritional and hormonal risk factors for prostate cancer. Biomarkers, including testosterone and insulin-like growth factor, and nutritional factors, especially meat, fat, and dairy intake, have been linked to greater risk of disease. Higher consumption of selenium and vitamin E, fructose/fruits, and tomatoes all have been associated with reduced occurrence of prostate cancer, but as yet their efficacy for prevention remains unproven. The challenge of understanding the enigmas of this disease will continue into future decades, as we convert current knowledge into preventive and therapeutic recommendations. Publication Types: Review Review, tutorial PMID: 9870033 [PubMed - indexed for MEDLINE]